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    Endotoxicity of lipopolysaccharide as a determinant of T-cell-mediated colitis induction in mice (2014)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Gronbach, Kerstin
    Flade, Isabell
    Holst, Otto
    Lindner, Buko
    Ruscheweyh, Hans Joachim
    Wittmann, Alexandra
    Menz, Sarah
    Schwiertz, Andreas
    Adam, Patrick
    Stecher, Bärbel
    Josenhans, Christine
    Suerbaum, Sebastian
    Gruber, Achim D (WE 12)
    Kulik, Andreas
    Huson, Daniel
    Autenrieth, Ingo B
    Frick, Julia-Stefanie
    Quelle
    Gastroenterology; 146(3) — S. 765–775
    ISSN: 0016-5085
    Sprache
    Englisch
    Verweise
    DOI: 10.1053/j.gastro.2013.11.033
    Pubmed: 24269927
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    Tel.+49 30 838 62450 Fax.+49 30 838 62522

    Abstract / Zusammenfassung

    The intestinal microbiota is an important determinant of the mucosal response. In patients with inflammatory bowel diseases, the mucosal immune system has inappropriate interactions with the intestinal microbiota. We investigated how the composition of the intestinal microbiota affects its endotoxicity and development of colitis in mice.

    Germ-free C57BL/6J-Rag(1tm1Mom) (Rag1(-/-)) mice were colonized with 2 different types of complex intestinal microbiota. Colitis was induced in Rag1(-/-) mice by transfer of CD4(+)CD62L(+) T cells from C57BL/6J mice. Colonic tissues were collected and used for histologic analysis and cell isolation. Activation of lamina propria dendritic cells and T cells was analyzed by flow cytometry.

    After transfer of CD4(+)CD62L(+) T cells, mice with intestinal Endo(lo) microbiota (a low proportion of Enterobacteriaceae, high proportion of Bacteroidetes, and low endotoxicity) maintained mucosal immune homeostasis, and mice with highly endotoxic Endo(hi) microbiota (a high proportion of Enterobacteriaceae and low proportion of Bacteroidetes) developed colitis. To determine whether the effects of Endo(hi) microbiota were related to the higher endotoxic activity of lipopolysaccharide (LPS), we compared LPS from Enterobacteriaceae with that of Bacteroidetes. Administration of Escherichia coli JM83 (wild-type LPS) to the mice exacerbated colitis, and Escherichia coli JM83 + htrBPG (mutated LPS, with lower endotoxicity, similar to that of Bacteroidetes) prevented development of colitis after transfer of the T cells to mice.

    The endotoxicity of LPS produced by the intestinal microbiota is a determinant of whether mice develop colitis after transfer of CD4(+)CD62L(+) T cells. This finding might aid the design of novel biologics or probiotics to treat inflammatory bowel disease.